Pediatric Cystic Fibrosis Population Research Articles

Extended Screening for Cystic Fibrosis-related Liver Disease Including Elastography in Children and Adolescents.

Advances in treatment of cystic fibrosis (CF) have increased survival and thereby prevalence of patients with liver disease, making chronic liver disease one of the major complications of CF. We describe the prevalence of liver fibrosis, portal hypertension, and liver decompensation by extended screening for cystic fibrosis-related liver disease (CFLD) including ultrasound, elastography, and an extended panel of biochemical markers. A cross sectional study of CFLD in all pediatric CF patients (1-18 years) from the Copenhagen CF Center. Screening for liver disease included physical examination, biochemical analysis, Vibration-Controlled Transient Elastography (FibroScan), conventional ultrasound, and Real-Time Shear Wave elastography (SWE). Patients were scored according to Williams ultrasound scoring scale (WUSS) within 6 months. A total of 84 consecutive patients (male sex 46.4%, median age 10.4 years) were included. Eight patients (9.5%) had both ≥2 abnormal results of sonographic methods and ≥2 abnormal biochemical results and were in this study categorized as having manifest CFLD. Manifest CFLD patients were significantly older and had a higher mean value of APRI, but no differences in gender, z-height, z-weight, z-BMI, FEV1%, or mean value of bilirubin or albumin were found. In total, 8 patients (9.5%) in this pediatric CF population were categorized as having CFLD according to both biochemical and sonographic tests. Consistency was found among the results of FibroScan and SWE. We suggest WUSS and either FibroScan or SWE, combined with GGT as diagnostic markers for CFLD.

Effects of CFTR modulators on pharmacokinetics of tobramycin during acute pulmonary exacerbations in the pediatric cystic fibrosis population.

Individuals with cystic fibrosis (CF) require higher dosages of aminoglycosides due to an increased volume of distribution (Vd ) and clearance. Optimal dosing of aminoglycosides in the CF population is essential as repeated exposure to aminoglycosides during acute pulmonary exacerbations increases risk of nephrotoxicity and ototoxicity. To date, no studies have evaluated whether chronic cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy affects pharmacokinetics of aminoglycoside antibiotics in patients with CF. The objective of this study was to determine if the addition of a CFTR modulator affects elimination rate (Ke ) for intravenously administered tobramycin in the pediatric CF population. This retrospective study included patients aged 2 to 18 years with CF receiving chronic therapy with a CFTR modulator. Patients included had an admission both pre- and post-chronic CFTR modulator therapy during which they received therapy with IV tobramycin. Thirty-four patients were included in the study. The median time between pre- and post-modulator admissions was 16.5 (13.8) months. Duration of CFTR modulator therapy before post-modulator admission was a median of 8 (10.3) months. There was no significant difference in Ke (hr-1 ) between pre- and post-modulator therapy, 0.41 (0.21) pre and 0.39 (0.09) post (P = .5). Vd and peak concentration were similar between both groups. There was no difference in nephrotoxicity as defined by the pRIFLE criteria (P = .25). The pharmacokinetic parameters of intravenously administered tobramycin during admission for acute pulmonary exacerbation do not appear to change significantly after initiating chronic therapy with a CFTR modulator. Empiric dose adjustments for patients on CFTR modulators are not recommended.

P374 Evaluation of anxiety levels in a paediatric cystic fibrosis population

P374 Evaluation of anxiety levels in a paediatric cystic fibrosis population

P389 The baseline psychological need of a paediatric cystic fibrosis population

P389 The baseline psychological need of a paediatric cystic fibrosis population

Middle ear disease in CF? It's not just about the sinuses anymore!

IntroductionHistorically cystic fibrosis (CF), in contrast to primary ciliary dyskinesia (PCD), has been considered protective of the middle ear from otitis media and rarely were such patients “severely affected” to require tympanostomy tube placement (BMT). Previously the Pittsburgh Otitis Media Research group reported a 10% prevalence of otitis media in the pediatric CF population which is significantly lower than age matched non-CF children. We studied the prevalence of OM in pediatric CF patients to assess if the otologic phenotype has changed in parallel with changes in the diagnosis itself. MethodsThe medical records of 133 CF patients seen either inpatient or outpatient from one of the largest tertiary pediatric CF centers in the world from 2010 to 2019 were reviewed for demographics, acute otitis media (AOM) episodes, risk factors for AOM, placement of myringotomy tubes, genotype, BMI, pancreatic status, respiratory culture results, and pulmonary exacerbations. ResultsJust over half (52.6%) the patients were male. A median age for CF diagnosis was 11 days old (range 0 days–16 years). The most common genotype (49.6%) was homozygous for ΔF508 mutation. Fifty-five (41.4%) patients had 1-2 episodes of AOM, and 15 (11.3%) were severely affected (i.e. ≥3 episodes/6 months or ≥4 episodes/year). COME was diagnosed in 4 (3.0%) of the patients. Twelve (9.0%) patients had tympanostomy tubes at least once, including 3 patients with multiple sets of tubes. Having at least one AOM episode was not predicted by genetic mutation groups, BMI, age at diagnosis, or comorbidities, p > .05. ConclusionsThe time-honored adage of CF protecting against otitis media is no longer true and pediatric otolaryngologists must now prioritize the management of middle ear disease as highly as sino-nasal and pulmonary disease. Future study into mechanisms explaining the change is needed.

A135 HEPATOLITHIASIS AND CHOLANGIOPATHY IN PEDIATRIC CYSTIC FIBROSIS: A CASE REPORT

Abstract Background Liver disease has emerged as an important cause of cystic fibrosis (CF)-associated morbidity due to recent advancements in management and a resultant increase in life expectancy. Although focal biliary cirrhosis remains the pathognomonic finding in CF, other hepatic manifestations exist but are not as well described, particularly in the pediatric population. Aims Present two rare manifestations of pediatric CF-associated liver disease. Methods In this report, we present a pediatric CF patient with chronic abdominal pain who was found to have hepatolithiasis, cholangitis and secondary sclerosing cholangitis. Results A 12-year-old boy with CF was seen for abdominal pain with functional impairment. He had prior evidence of calculi in the common bile duct (CBD) and right intrahepatic (IH) duct, and had undergone endoscopic retrograde cholangiopancreatography (ERCP) twice with sphincterotomy once. Magnetic resonance cholangiopancreatography (MRCP) at presentation showed dilated CBD and bilateral IH ducts with calculi, evidence of acute cholecystitis and early cholangitis. He subsequently underwent a third ERCP with stone retrieval, stent placement and a laparoscopic cholecystectomy. Ursodiol dose was optimized and antibiotics were initiated. Follow-up MRCP showed improvement in CBD and IH duct dilation; the stent was removed. One month later, a fifth ERCP was performed for worsening symptoms associated with a distal filling defect in the left IH duct. Sludge was removed from the CBD and another stent was placed. A sixth ERCP with stent removal showed no stones. Interval MRCP showed resolution of IH calculi, a CBD filling defect suggestive of sludge, and thickening and enhancement of IH bile ducts with focal areas of alternating narrowing and dilation. He was maintained on antibiotics, and his symptoms persisted over the following months despite resolution of sludge, peri-portal edema and duct-wall enhancement. There was a background of increased IH ductal dilation with “beaded appearance”. Interval imaging has demonstrated persistence of these findings with recurrence of hepatolithiasis in both IH ducts, despite improved symptoms. Conclusions This case describes two rare manifestations of pediatric CF-associated liver disease: hepatolithiasis and secondary sclerosing cholangitis. While CFTR dysfunction alone predisposes to gallstone formation, the patient’s clinical course supports a theory for the development of hepatolithiasis resembling that of recurrent pyogenic cholangitis, whereby bacteriobilia from chronic or recurrent infection may promote lithogenesis in the presence of inflammatory bile duct damage. In this patient, secondary sclerosing cholangitis may have resulted from cycles of cholangitis and hepatolithiasis; alternatively, it may represent under-recognized cholangiopathy in the pediatric CF population. Funding Agencies None

Impact of health-system specialty pharmacy services on medication adherence in pediatric patients with cystic fibrosis

Background: Specialty medications represent a growing part of the pharmacological management of chronic disease states such as cystic fibrosis (CF). The management of CF in the pediatric population is complex, as it involves multiple medications and treatment success is largely determined by adherence to the care plan. There is often a delay between prescribing of specialty medications and initiation of therapy in the pediatric CF population. Health-system specialty pharmacy services provide significant benefits when compared to external specialty pharmacies, including direct access to the medical record, collaboration with the healthcare team, continuous patient education and continuity of care. Aims: The objective of this initiative was to assess the impact of Outpatient Pharmacy Services at Yale New Haven Health (OPS), a health system specialty pharmacy, on medication adherence in pediatric patients with CF. Methods: A prospective review of 65 pediatric patients with CF seen by the pharmacist in a health-system CF clinic over 6 months was conducted for medication adherence and compared to a retrospective cohort. Education about the health-system specialty pharmacy services was provided to patients through the following methods: invitation letter, informational pamphlets distributed in clinic and direct education by the clinic pharmacist. A clinic workflow was implemented to streamline the referral process. Primary endpoints include: medication possession ratio (MPR), proportion of days covered (PDC), and percentage of prescriptions sent to and filled by the OPS. Results: A total of 65 pediatric CF prescriptions were written from September 2017 to February 2018, with only 7.7% of the prescriptions sent to OPS prior to implementation of the clinic workflow. The MPR and PDC in this retrospective cohort were 0.85 and 0.75 respectively. From September 2018 to February 2019 the number of prescriptions for all medications written was 304, with 32.9% sent to OPS and a fill rate of 89%. The MPR and PDC for that year were 0.86 and 0.80 respectively. Conclusions: This single-center review that assessed the impact of specialty pharmacy services on pediatric patients with CF in a large health system demonstrated improved and sustained patient medication adherence. The increase in utilization of OPS led to an increase in prescriptions received and filled by the health-system specialty pharmacy.

EPS4.09 A retrospective review of iron status and supplementation in a paediatric regional cystic fibrosis population

ePS4.09 A retrospective review of iron status and supplementation in a paediatric regional cystic fibrosis population

P326 Are combined vitamin preparations useful in a paediatric cystic fibrosis population?

P326 Are combined vitamin preparations useful in a paediatric cystic fibrosis population?

P429 Does the number of TIVAD devices inserted reflect our perception that the health of our paediatric cystic fibrosis population is improving?

P429 Does the number of TIVAD devices inserted reflect our perception that the health of our paediatric cystic fibrosis population is improving?

Incidence and risk factors of paediatric cystic fibrosis-related diabetes

IntroductionCystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF) directly linked to increased morbidity and mortality. Both the incidence of type I and type II diabetes has been shown to increase in the general population. In this study, we investigated the incidence and risk factors of CFRD in a paediatric CF population. MethodsProspectively collected data from the Canadian CF Registry (CCFR) from 2000 to 2016 for patients ages 10 to 18 years was used to determine the incidence of CFRD. Risk factors for CFRD in the Canadian population were investigated using a nested case-control design. Conditional logistic regression analysis with a 4:1 control: case matching was used. ResultsFrom 2000 to 2016, 2326 patients with CF aged between 10 through 18 years were included in the CCFR, during this time the overall incidence rate of CFRD was 2.1 cases per 100 patient-years (95% confidence interval 1.8 to 2.3). Incidence rates were stable in the Canadian cohort over three consecutive time periods 2000–2005, 2006–2010; 2011–2016. Worse lung function, female gender, history of allergic bronchopulmonary aspergillosis, Gastrostomy tube insertion and liver disease were statistically significant risk factors for CFRD. ConclusionThe incidence of CFRD in the Canadian paediatric population has been stable over time, in contrast to the rising rates of Type 1 and Type 2 diabetes in the general paediatric population. The risk factor for CFRD in this contemporary population were consistent with previous studies.

An Exploration Into Knowledge, Attitudes, and Beliefs Towards Risky Health Behaviours in a Paediatric Cystic Fibrosis Population.

Risky behaviours are prevalent within the cystic fibrosis (CF) population; however, there is a lack of research which has investigated risky behaviour engagement among adolescents with CF, with reasons for initiation currently being unknown, as no qualitative studies have been conducted. This research therefore examines knowledge, attitudes, and beliefs towards risky behaviours at an age commonly associated with initiation. Ten paediatric participants were recruited. Thematic analysis illustrated several psychological factors associated with risky behaviours. A desire for normalcy was evident, with this been associated with a desire to engage in normalised risky behaviours. Evidence of a life-orientated illness perspective was also prevalent, with participants believing that many individuals engage in risky behaviours for fun. Overall, there was a reported lack of knowledge on consequences of risky behaviours, with many participants not being informed of these by health care professionals (HCPs). This research provides insight into an area of CF paediatric care which could be improved on, with the provision of awareness regarding risky behaviours not being embedded within paediatric CF care. Consequently, this research demonstrates the need for interventions to be integrated into paediatric CF care for the prevention and reduction of risky behaviours.

Epidemiology of Nontuberculous Mycobacteria Infection in Children and Young People With Cystic Fibrosis: Analysis of UK Cystic Fibrosis Registry.

BackgroundInfection with nontuberculous mycobacteria (NTM) is of growing clinical concern in people with cystic fibrosis (CF). The epidemiology of infection in children and young people remains poorly understood. Our goal was to investigate the epidemiology of NTM infection in the pediatric age group using data from the UK CF Registry.MethodsData from 2010–2015 for individuals aged <16 years (23200 observations from 5333 unique individuals) were obtained. Univariate analysis of unique individuals comparing all key clinical factors and health outcomes to NTM status was performed. The significant factors that were identified were used to generate a multivariate logistic regression model that, following step-wise removal, generated a final parsimonious model.ResultsThe prevalence of individuals with a NTM-positive respiratory culture increased every year from 2010 (45 [1.3%]) to 2015 (156 [3.8%]). Allergic bronchopulmonary aspergillosis (odds ratio [OR], 2.66; P = 5.0 × 10−8), age (OR, 1.08; P = 3.4 × 10−10), and intermittent Pseudomonas aeruginosa infection (OR, 1.51; P = .004) were significantly associated with NTM infection.ConclusionsNTM infection is of increasing prevalence in the UK pediatric CF population. This study highlights the urgent need for work to establish effective treatment and prevention strategies for NTM infection in young people with CF.

Evaluation of the safety of piperacillin/tazobactam use in admitted pediatric patients with cystic fibrosis

Background: Piperacillin/tazobactam (PT) is a first-line antibiotic for Pseudomonas aeruginosa (PsA) respiratory infections in patients with cystic fibrosis (CF), but increased adverse reactions (ARs) have been reported in these patients. We aimed to determine the incidence of and risk factors for ARs to PT within the pediatric CF population. Methods: We conducted a retrospective analysis of CF patients at a pediatric tertiary care centre who had received PT and compared ARs associated with PT versus other antipseudomonal antibiotics. Results: Of the 26 patients who received PT, the PT AR prevalence was n=7 (27%); 3 patients developed fever and rash, 2 had only fever, 1 had only rash, and 1 had fever, rash, and severe neutropenia. The following variables were associated with fever following PT administration: younger age (8.46 versus 13.15 years, p=0.02), fewer previous admissions for CF pulmonary exacerbation (1.67 versus 7.25, p=0.03), and increased PT dose (386.37 versus 270.73 mg/kg/day, p=0.02). Younger age was also associated with increased overall AR to PT (9.6 versus 13.3 years, p=0.04). Increased PT dose was associated with fever (OR 1.02 (1.00–1.05), p=0.03) and with overall reactions (OR 1.01 (1.00–1.02), p=0.03). Comparing incidence rates of ARs following PT and ticarcillin/clavulanate resulted in a trend toward increased relative reaction to PT, but confidence intervals (CIs) were not significant. Conclusions: We found a high AR rate associated with PT, and an association between increased dose and fever and overall ARs.

399 - Single High-Dose Oral Vitamin D3 (Stoss Dose) in Lieu of Daily Dosing is Reliably Effective for Treatment of Vitamin D Insufficiency/Deficiency in Pediatric Hematopoetic Stem Cell Transplant (HSCT) Recipients

Background: It is estimated as many as 70% of children in the United States have deficient or insufficient vitamin D levels. Pediatric HSCT recipients are particularly at high risk for deficiency due to sun avoidance and sunscreen use, malabsorption, and increased catabolism due to steroid and/or calcineurin inhibitor use. It has also been postulated that maintaining adequate vitamin D levels can impact outcomes such as engraftment, graft-versus-host disease, and rejection. Given their complex medication regimens, addition of a daily vitamin D maintenance dose may lead to non-adherence and an inability to achieve adequate levels. Methods: This was a retrospective single-center analysis of pediatric HSCT recipients that received single high-dose oral vitamin D therapy beginning in May 2014. Vitamin D deficiency was defined as a 25-hydroxyvitamin D (25(OH) D) level below 20 ng/mL and insufficiency as a level of 21-29 ng/mL. The patients received doses according to dosing guidelines established in the pediatric Cystic Fibrosis population at this institution, adapted from the study by Shepherd et al in 2013. (Table 1)Table 125-OH Vit D Level (ng/mL)<3 yrs3-12 yrs>12 yrs≤ 10200,000 units400,000 units600,000 units10-20150,000 units350,000 units500,000 units20-30100,000 units200,000 units300,000 units Open table in a new tab Results: There were 14 patients identified as having received vitamin D stoss therapy and 20 doses administered. All patients evaluated had received allogeneic HSCT. In patients for whom follow-up levels were available (n = 17), an average increase in 25(OH) D level of 21 ng/mL was observed. In patients that received multiple doses, (n = 3) there was an average of 90.6 days between administrations. Two patients in the study group had follow-up levels decrease following stoss therapy, likely attributed to critical illness at the time of administration. No toxicities associated with high-dose vitamin D administration were observed. Conclusion: Single high-dose oral vitamin D therapy is an effective method for restoring and maintaining adequate vitamin D levels in this patient population. This approach reduces the need for the addition of a daily maintenance medication and allows for controlled, periodic dosing and monitoring.

Medications used in pediatric cystic fibrosis population.

ABSTRACTObjective To describe the drug utilization profile used by pediatric cystic fibrosis patients.Methods A transversal study comprising the analysis of records and interviews with caregivers of pediatric patient in a reference center of Southern Brazil. We collected information about patients’ clinical condition, medication used and household therapy.Results Out of 78 patients participating in the study, prevailing characteristics were: female, self-declared white color, mutation F508del and countryside resident. Forty-three patients had health monitoring exclusively in the hospital’s outpatient division. We analyzed 509 prescribed medication (6.5 medication/patient). The caregiver acknowledged the correct indication in 83% of cases. Patients with pulmonary complications and diseases and/or comorbities related to the cystic fibrosis had an increased quantity of prescribed medication. Vitamins, pancreatic enzymes, hypertonic saline solution, dornase alpha, acid ursodesoxicolic and inhalation antibiotics were most commonly prescribed. Out of the sum of medication, 265 (52.1%) were registered in the Relação Nacional de Medicamentos Essenciais , 26.7% were registered in the basic component and 25.4% were registered in the specialized component of pharmaceutical assistance. Seventy-four interviewees informed difficulty in the acquisition of at least one prescribed medication. Most of the reports acknowledge the State Health Department as the place to find and receive medication for cystic fibrosis.Conclusion This study allowed reaching a deeper understanding about therapy, caring needed with patients with cystic fibrosis, highlighting to implement strategies that might contribute to enhance life quality and to execute the patients’ therapy plan.

Frequency of small-colony variants and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in cystic fibrosis patients

BackgroundSmall-colony variants (SCVs) are a distinct phenotype of Staphylococcus aureus, known for their role in chronic, difficult to treat infections, including cystic fibrosis (CF) lung disease. The goal of this study was to characterize SCV MRSA infection in an adult and pediatric CF population and to identify antibiotic susceptibility patterns unique to SCV MRSA. MethodsWe recovered methicillin-resistant S. aureus (MRSA) from respiratory culture samples from CF patients at the Johns Hopkins Hospital during a 6month study period. ResultsOf 1161 samples, 200 isolates (17%) were identified as MRSA, and 37 isolates from 28 patients were identified as SCV MRSA. A higher proportion of MRSA was found among SCV isolates (37/66, 56%) compared to normal colony variant (NCV) isolates (163/417, 39%), p=0.02. All SCV MRSA isolates from individual patients were susceptible to vancomycin and ceftaroline, but they demonstrated higher rates of antibiotic resistance to trimethoprim/sulfamethoxazole, moxifloxacin, and erythromycin, compared to NCV MRSA isolates. Additionally, individuals with SCV MRSA had lower lung function, higher rates of persistent MRSA infection, and higher rates of previous antibiotic use, compared to individuals with NCV MRSA. ConclusionsA significant proportion of MRSA isolates recovered from patients with CF have the SCV morphology. Compared to individuals with NCV MRSA, those with SCV MRSA have higher rates of persistent MRSA infection and lower lung function. SCV MRSA isolates were more resistant than NCV, but they are highly susceptible to vancomycin, linezolid and ceftaroline.

Safety of intravenous tobramycin in combination with a variety of anti-pseudomonal antibiotics in children with cystic fibrosis.

Objectives:Previous studies have examined renal safety of once daily intravenous tobramycin in individuals with cystic fibrosis. This has been mainly in combination with ceftazidime in an adolescent or adult population. In this report, we describe our institutional experience of once daily intravenous tobramycin in combination with a variety of second anti-pseudomonal antibiotics in children with cystic fibrosis.Methods:We present a retrospective review including children with cystic fibrosis, who were admitted for a pulmonary exacerbation from January 2009 to December 2011, and treated using intravenous tobramycin. A literature review of once daily intravenous aminoglycoside dosing in cystic fibrosis was performed to compare our results to existing literature.Results:A total of 35 subjects were divided into once daily dosing (n = 20) versus multiple daily dosing (n = 15) groups. Mean age was 11.3 years (± 5.7) for the once daily dosing group and 13.1 years (± 4.4) for the multiple daily dosing group (p = 0.34). All subjects had normal baseline serum creatinine at admission (once daily dosing 0.49 ± 0.14 mg/dL vs multiple daily dosing 0.62 ± 0.23 mg/dL, p = 0.07). All subjects received intravenous tobramycin, and most received piperacillin-tazobactam as their second anti-pseudomonal antibiotic (once daily dosing 45% and multiple daily dosing 40%). There was no significant change in serum creatinine in either group during antibiotic treatment (once daily dosing 0.08 ± 0.12 mg/dL vs. multiple daily dosing 0.06 ± 0.10 mg/dL, p = 0.43). All subjects had significant improvement in lung function following intravenous antibiotic therapy.Conclusion:We show that both once daily dosing and multiple daily dosing of intravenous tobramycin in combination with a variety of second anti-pseudomonal antibiotics were safe in terms of nephrotoxicity in children with cystic fibrosis. These findings are important given existing literature mainly examines once daily tobramycin in combination with ceftazidime, a cephalosporin, and the majority of our patients were on tobramycin with piperacillin-tazobactam, an extended spectrum penicillin plus beta-lactam. This contributes new information not previously examined in a pediatric cystic fibrosis population.

Evaluating the sinus and Nasal Quality of Life Survey in the pediatric cystic fibrosis patient population

IntroductionThe Sinus and Nasal Quality of Life Survey (SN-5) is a validated quality of life (QOL) questionnaire for chronic rhinosinusitis in patients age 2–12. Its utility in the cystic fibrosis (CF) has been studied, but not yet validated. The purpose of this study is to determine the effectiveness of the SN-5 for evaluation of sinonasal symptoms in the pediatric CF population. MethodsThis retrospective study analyzed SN-5 surveys completed between 2012 and 2015 by pediatric CF patients and caregivers. Baseline and follow-up overall QOL scores and specific symptom scores were obtained from surveys completed in the three-year span. Non-parametric statistics were conducted to identify differences in survey data. ResultsA total of 165 patients completed baseline and follow-up surveys. The overall QOL of the patient cohort did not change over the duration of the study (p = 0.660). Thirty-seven patients indicated higher overall QOL, with all five symptom scores showing significant improvement. Analysis by age group showed that QOL was significantly correlated with all five symptoms for children ages 0–4. In patients 5–12 years, overall QOL was only correlated with sinus infection (r = −0.3090, p = 0.01). QOL was significantly correlated with sinus infection (r = −0.2903, p = 0.04) and allergy symptoms (r = −0.5644, p < 0.01) in patients >12 years of age. ConclusionThere remains a need for a validated CRS QOL tool for children with CF. Though the SN-5 has previously been described as a potential instrument, our data suggest that it may be more valuable in children ages 0–4.

265 Tolerance of dry powdered inhaled (DPI) antibiotics in a paediatric cystic fibrosis population

265 Tolerance of dry powdered inhaled (DPI) antibiotics in a paediatric cystic fibrosis population